Micro RNAs (miRNAs) are a class of small regulatory non-coding RNAs (22 nt) that are evolutionary conserved and have been shown to be extensively involved in posttranscriptional regulation of mRNAs [1]. miRNAs bind to partially complementary target sites in the 3′UTR of their target mRNAs which leads either to mRNA degradation or translational repression, depending on the grade of complementary. In animal cells, degradation of partially complementary miRNA targets occurs via deadenylation followed by decapping and subsequent exonucleolytic digestion [2-4]. In human over 600 miRNAs have been identified and it has been estimated that ≈30% of protein coding genes are regulated by miRNAs [5]. miRNAs have crucial functions for basic cellular processes like differentiation or apoptosis, normal cellular development, but also play important roles in the pathogenesis, especially cancer. Several miRNAs have been described to act as oncogenes or tumor suppressors [6-8]. mRNAs have also been shown to participate in pathogenesis and disease progression in cancer. Prostate cancer (PCa) is the most frequently diagnosed malignancy and second leading cause of cancer death in men, with strongly varying rates of tumor progression and responses to treatment [9]. The etiology of PCa is multifactorial, involving environmental and genetic factors [10]. PCa is strongly associated with aging and 2 out of 3 cases are diagnosed in men older than 65 years of age [11]. Treatment of prostate cancer varies depending on the stage of the disease [12]. Early stages of PCa are clinically well manageable. For metastatic forms of prostate cancer the role of androgen deprivation as a firstline therapy has been recognized for more than 60 years [13,14], as initially almost all metastatic prostate cancers require testosterone for growth. Initial response rates to androgen depletion therapy are high, but patients generally progress to a clinically androgen-independent state of the disease within 18-24 months, which results in death within 16 to 18 months. [15-20]. For this metastatic, hormone-refractory (“castration-resistant”) form of the disease, no curative therapy exists today.
Therefore, identifying miRNAs that are deregulated in PCa may lead to a better understanding of the etiology of the disease, may deliver markers for diagnosis and prognosis and last but not least may provide novel therapeutic strategies, in particular for fighting the advanced forms of the disease. Several miRNA expression studies in PCa have been published [21-25] showing an overall downregulation of miRNAs in cancer with a more pronounced decrease in more advanced stages, while only two miRNAs have been found to be upregulated in PCa [26-29].
It is thus one object of the present invention to provide novel, mi-RNA-based pharmaceutical compositions for the treatment of prostate cancer.